From jan@Acadia-Pharm.com Sun Mar 1 07:15:02 1998 Received: from rtec01.receptortechnologies.dk for jan@Acadia-Pharm.com by www.ccl.net (8.8.3/950822.1) id GAA10463; Sun, 1 Mar 1998 06:48:43 -0500 (EST) Received: from THC by rtec01.receptortechnologies.dk with SMTP (Microsoft Exchange Internet Mail Service Version 5.0.1458.49) id F4LYBPTM; Sun, 1 Mar 1998 12:47:26 +0100 Date: Sun, 1 Mar 1998 12:40:57 +0100 (MET) From: Jan Pedersen To: chemistry@www.ccl.net Subject: pKa calculations - digest of replies Message-ID: MIME-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII Content-Transfer-Encoding: QUOTED-PRINTABLE Greetings all CCLers, Some tile ago I sent out a request for methods to calculate pKa values for small molecules. I have received quite a lot of responses and requests for some sort of digest of the responses. I am in the process of evaluating all the methods that I can get my hands on using a set of toy molecules. Here is currently a poor digest of the replies - for further information on the individual methods - please contact the primary source. =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D A small survey about methods for pKa calculations on small organic compounds. Jan T Pedersen =09=09(Feb. 1998)=09jan@acadia-pharm.com =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D Dr. Mike Gilson (co-author of UHBD) gilson@indigo14.carb.nist.gov ------------------------------ Klopman and Fercu, JCC 15:1041, 1994. (This describes a QSAR used to predict the pKas of 2500 organic acids). Dixon and Jurs, JCC 14:1460, 1993. "Estimation of pKa for organic oxyacids using calculated atomic charges". (They have another paper that prescribes how to compute the atomic charges, I think.) Finally, some series of analogs can be handled reasonable well with classical e-static models. You'd need to know the pKa of one of the group; the e-static model would then be used to predict the influence of adding or removing polar groups. This might not work so well, however, if the added groups are very close in bonding sequence to the group whose pKa you want... because the model does not capture through-bond inductive effects. QM methods reference : =20 Richardson et al, JCC 61:207-217, 1997 =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D Jens Spanget-Larsen jsl@virgil.ruc.dk ------------------- Claims to have good references in :=20 J. Spanget-Larsen: "Structure-reactivity correlations for aza-arenes.=20 Proton affinities, pKa values, hydrogen-deuterium exchange rates and=20 radical induced C-13 shifts", Journal of Physical Organic Chemistry,=20 Vol. 8, pp 496-505 (1995). =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D Morten Langg=E5rd MOL@Lundbeck.com ---------------- Uses a program called MolSurf written by P=E4r Sj=F6berg, can be obtained b= y writing to par.sjoberg@mbox309.swipnet.se. Uses Spartan or Gaussian output to calculate a number of different parameters, eg. pKa. =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D David E. Clark David-E.Clark@rp-rorer.co.uk Victoria Barclay victoria@acdlabs.com ---------------------------- Several people have identified the ACD Labs program: Regarding commercial software for pKa calculations, you might be interested in our ACD/pKa DB or related software... please see: http://www.acdlabs.com/products/pka/ The algorithm is described on the page: http://www.acdlabs.com/products/pka/pka_algo.html =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D Andreas Goeller goeller@pc04.chemie.uni-jena.de Andy Holder aholder@cctr.umkc.edu Shawn Butler shawn@wavefun.com ------------------------------- Andreas Goeller writes: Is using semiempirical packages ampac and vamp. It seems that one can eventually getting pka values by scaling the results of=20 SH + H2O ---> B + H3O+ You have to calculate dG =3D dHf(0K) + ZPE+ (dH-TdS (300K))+ dGsolv then log K =3D -dG/2.303RT See also the article J Phys Chem 101, 1997, 2959 Andy Holder writes: Our packages AMPAC and CODESSA will do this quite well. AMPAC is an excell= ent=20 general purpose semiempirical quantum mechanical program with a graphical u= ser=20 interface. CODESSA is a QSAR/QSPR program that uses data from AMPAC to=20 compute over 500 descriptors and perform advanced statistical analysis to= =20 derive correlations for a variety of purposes. I will send a packet with s= ome=20 brochures and papers describing our products along with some reprints=20 describing the use of CODESSA with AMPAC. In the meantime, you can examine= =20 our website at http://www.semichem.com. =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D Ole Hvilsted oho@novo.dk ------------ Identified the PALLAS program from CompuDrug. This program can be obtained together with a test license from ftp.compudrug.hu. Mor information can be obtained by mailing to mktg@cdk-cgx.hu. =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D Gerald Loeffler LOEFFLER@bender.co.at --------------------- Has identified the DelPhi program from MSI and MEAD from Bashford. More info about these packages can be found on the web at : http://www.msi.com http://www.scripps.edu/bashford/index.html =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D Brian Teppen teppen@srel.edu --------------- Dr. Sam Karickhoff of the US Environmental Protection Agency has developed such a program, which I believe is called SPARC. A relevant paper is=20 Hilal, S.H., L.A. Carreira, G.L. Baughman, S.W. Karickhoff and C.M. Melton. 1994. Estimation of Ionization Constants of Azo Dyes and Related Aromatic Amines: Environmental Implication. Journal of Physical Organic Chemistry 7(3):122-141. The program is probably free of charge, and reasonably well tested and documented. ----------------------------------------------------------- =09=09=09Dr. Jan T. Pedersen=09 =09=09=09Head, Computational Chemistry =09=09=09Acadia Pharmaceuticals =09=09=09Fabriksparken 58 =09=09=092600 Glostrup, DENMARK =09=09=09email : jan@Acadia-Pharm.com =09=09=09phone : +45 43 29 30 05 =09=09=09FAX : +45 43 29 30 30 =09=09=09Lore : http://www.acadia-pharm.com ----------------------------------------------------------- From jlye@tx.ncsu.edu Sun Mar 1 22:15:08 1998 Received: from sparc20.tx.ncsu.edu for jlye@tx.ncsu.edu by www.ccl.net (8.8.3/950822.1) id VAA13139; Sun, 1 Mar 1998 21:40:52 -0500 (EST) From: Received: (from jlye@localhost) by sparc20.tx.ncsu.edu (8.8.4/UC02Jan97) id VAA04423 for chemistry@www.ccl.net; Sun, 1 Mar 1998 21:40:41 -0500 (EST) Message-Id: <199803020240.VAA04423@sparc20.tx.ncsu.edu> Subject: semi-empirical spelling To: chemistry@www.ccl.net Date: Sun, 1 Mar 1998 21:40:38 -0500 (EST) X-Mailer: ELM [version 2.4 PL24/POP] MIME-Version: 1.0 Content-Type: text/plain; charset=US-ASCII Content-Transfer-Encoding: 7bit Dear Netters, I am in the middle of writing my Ph.D. thesis and also a couple of papers on molecular modeling of dyes using semi-empirical methods. My question is, how do you spell semi-empirical - with or without the hyphan? Some authors prefer semiempirical. I can't find it in the dictionary. Also, in the title of the paper, should I put ....Semi-Empirical... or Semi-empirical...? Thanks for your advice, Jason _______________________________________________________________________________ Jason Lye, | Dye Synthesis Research Group, | College Of Textiles, Box 8301, | "Too much of a North Carolina State University, | good thing is wonderful" Raleigh, N.C. 27695 - 8301 | | - Mae West. Ph: (919) 515-6615 | jlye@tx.ncsu.edu | _______________________________________________________________________________